Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer

Abstract

Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided.

The Treatment of Advanced Thyroid Cancer in the Age of Novel Targeted Therapies

“…In addition to its utility in the adjuvant setting, RAI can also be used as effective systemic therapy for patients with unresectable or metastatic DTC, so long as tumor cells maintain the ability to take up and concentrate 131 I [3,6,8]. In 5–15% of patients with DTC, however, this ability is lost and the tumor is classified as refractory to RAI (RAIR) [9–12]. Although outcomes in DTC are generally excellent, with 5-year overall survival reported at 97.8 % [2], the 5-year disease specific survival for patients with RAIR DTC is 66%, and 10-year survival is only 10% [9].…”

“…In 5–15% of patients with DTC, however, this ability is lost and the tumor is classified as refractory to RAI (RAIR) [9–12]. Although outcomes in DTC are generally excellent, with 5-year overall survival reported at 97.8 % [2], the 5-year disease specific survival for patients with RAIR DTC is 66%, and 10-year survival is only 10% [9]. Patients with RAIR DTC and distant metastasis survive approximately 2.5 – 3.5 years [9,94].…”

Current status of differetiated radioactive iodine-resistant thyroid cancer: case report of successful long-term treatment with sorafenib

“…Например, в исследовании DECISION, у 17% па-циентов, получавших плацебо, выживаемость без прогрессирования была более чем 1 год [40]. Кро-ме того, в группе пациентов с «нечувствительны-ми» очагами по ПЭТ с ФДГ медиана выживаемости составила 41 месяц без таргетной терапии [41].…”

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

“…For patients with smaller tumors that are rapidly progressing (< 6-12 months) or for those who have large tumors that progress slowly ( > 12 months), the decision to treat or not (or to postpone treatment) is less clear and should be considered on a case-by-case basis (6,26,27).…”